Clinical Trials

Question 1

What do clinical trials provide evidence of?

Answer 1

Drugs are safe and effective

Question 2

How many prescriptions do GPs give out per day on average?

Answer 2

70

Question 3

How much does the NHS spend on drugs each year?

Answer 3

£11.7 billion

Question 4

What are examples of drugs that were developed before clinical trials were required, what does this explain?

Answer 4

Warfarin and digoxin which is why they have so many side effects

Question 5

What is an observational study?

Answer 5

Observes individuals without manipulation or intervention

Question 6

What are some problems with observational studies?

Answer 6

False positives

Replication is difficult due to bias/different criteria

Question 7

What do clinical trials prove (in terms of putting theory into practice)?

Answer 7

What works in theory might not work in practice

Question 8

Why does the process of getting a drug onto the market take years?

Answer 8

Need to go through all of the stages to be approved for a license

Question 9

Who are clinical trials regulated by?

Answer 9

MHRA

Question 10

What is tested during clinical trials?

Answer 10

Safety

Efficacy

Question 11

How is the efficacy of a drug compared?

Answer 11

With placebo or another drug

Question 12

What are some laws which cover drug trials?

Answer 12

UK Medicines Act 1968

The Medicines for Human Use (Clinical Trials) Regulations 2004 and 2014

Question 13

What are the stages of drug development?

Answer 13

1) Drug discovery
2) Pre-clinical development
3) Clinical development

Question 14

What is tested during pre-clinical development?

Answer 14

Amimal pharmacology

Animal toxicity

Tissue culture

Question 15

What are the stages of clinical development?

Answer 15

1) Phase 1 (volunteer studies)
2) Phase 2 (given to patients)
3) Phase 3 (formal therapeutic trials)
4) Phase 4 (post marketing surveillance)

Question 16

What is tested during phase 1 trials?

Answer 16

Clinical pharmacology in normal volunteers

Question 17

How many subjects are used in phase 1?

Answer 17

100

Question 18

What happens during phase 2?

Answer 18

Clinical investigations in patients to confirm kinetics and dynamics

Evidence of efficacy and likely dosage range

Question 19

How many subjects are used during phase 2?

Answer 19

Up to 500

Question 20

What happens during phase 3?

Answer 20

Formal therapeutic trials establish efficacy and evidence of safety

All data submitted as an application for a license to sell the drug

Question 21

How many subjects are used during phase 3?

Answer 21

1000 - 3000

Question 22

What happens during phase 4?

Answer 22

Post marketing surveillance to produce evidence of long term safety

Question 23

How many people can phase 4 involve?

Answer 23

Tens to hundreds of thousands

Question 24

When do tegenero trials happen?

Answer 24

During phase 1

Question 25

What are tegerno trials?

Answer 25

Involves 8 patients: 6 given drug intravenously 2 given placebo

Question 26

What do pilot studies test and what do they not test?

Answer 26

They do not test outcome but test the study design

Question 27

What are examples of different pilot studies?

Answer 27

Double blind Single blind Prospective Retrospective

Question 28

What is a double blind study?

Answer 28

Patient and doctor are blinded

Question 29

What is a single blind study?

Answer 29

Patient is blinded

Question 30

What is a prospective study?

Answer 30

Protocol is decided beforehand

Question 31

What is a retrospective study?

Answer 31

Looks backwards and examines exposure to risk factors in relation to outcome that are established at the start of the study

Question 32

What can different studies involve comparisions with?

Answer 32

Placebo Other therapy Cross over design

Question 33

What is a cross over design?

Answer 33

Patient is given additional treatment which is being tested

Question 34

What is a randomised control study?

Answer 34

One where patients are assigned to one of the groups at random

Question 35

What are some disadvantages of randomised control?

Answer 35

Generalised (subjects may not represent patient population) Recruitment (twice as many new patients needed for the study) Acceptability (some physicians or patients will refuse) Administrative complexity (randomisation methods etc)

Question 36

What does superiority design show?

Answer 36

New treatment is better than the control or standard treatment

Question 37

What does non-inferiority design show?

Answer 37

Not worse than standard treatment by more than some margin Would have beaten placebo if it had been included

Question 38

What should the end points of a design be?

Answer 38

Simple, such as: Death Number of hospital admissions Lowering of blood pressure

Question 39

What do you need to consider when designing a study?

Answer 39

Choice of subjects (enough to be able to detect or reject differences between groups) Choice of control drug (placebo or another drug) Choice of patients (age, race, sex, diseases and drugs) Exclusion and selection criteria (pregnant woman, children, seriously ill patients, elderly)

Question 41

What are challenges with trials that involve the elderly?

Answer 41

They usually have multiple conditions

Question 42

What do you need to consider when analysing and interpreting data?

Answer 42

Statistical test Are differences due to chance O\<0.05 usually taken as significance

Question 43

What are some ethics that must be considered?

Answer 43

Consent Ethics committee Placebos Children

Question 44

How long can overall development of the drug from initial research to its first launch take?

Answer 44

Up to 20 years

Question 45

What is post marketting surveillance done by?

Answer 45

Medicines and Healthcare devices Regulatory Authority (MHRA) Yellow card system